External Evaluation of Population Pharmacokinetics and Pharmacodynamics in Linezolid-Induced Thrombocytopenia: The Transferability of Published Models to Different Hospitalized Patients
External Evaluation of Population Pharmacokinetics and Pharmacodynamics in Linezolid-Induced Thrombocytopenia: The Transferability of Published Models to Different Hospitalized Patients
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DOI：
10.1097/ftd.0000000000000816
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发表时间：
2021-04-01
影响因子：
2.5
通讯作者：
Yamamoto, Yoshihiro
中科院分区：
文献类型：
--
作者：
Ogami, Chika;Tsuji, Yasuhiro;Yamamoto, Yoshihiro
背景资料：本研究的目的是对已发表的利奈唑胺群体药代动力学和药效学模型进行外部评价，以使用独立数据集评价预测性能。另一个目的是提供一个优雅的环境，用于显示和模拟利奈唑胺给药后的浓度和血小板计数。研究方法：我们在PubMed中对所有评价利奈唑胺在患者中的群体药代动力学和药效学参数的研究进行了系统性文献检索，并选择了用于外部验证的模型。通过绘制预测误差（PE）和相对PE，目视评估预测偏倚。通过计算平均绝对误差（MAE）、均方根误差（RMSE）和平均相对误差（MRE）评价预测精度。结果如下：3篇文章（模型A、B和C）使用群体药代动力学和药效学建模方法提供了利奈唑胺诱导的血小板动力学模型。模型A和C的利奈唑胺浓度和血小板计数的PE和相对PE显示出相似的预测分布。关于总利奈唑胺浓度的预测准确度，模型C群体预测值的MAE、RMSE和MRE最小。3种药效学模型的患者-个体预测值的MAE、RMSE和MRE比较显示无较大差异。结论：我们证实了已发表的群体药代动力学和药效学模型的可转移性，并表明它们适合外推到其他医院和/或患者。本研究还介绍了基于C模型的利奈唑胺治疗药物监测应用软件。
Background: The objective of this study was to perform an external evaluation of published linezolid population pharmacokinetic and pharmacodynamic models, to evaluate the predictive performance using an independent data set. Another aim was to offer an elegant environment for display and simulation of both the concentration and platelet count after linezolid administration. Methods: We performed a systematic literature search in PubMed for all studies evaluating the population pharmacokinetic and pharmacodynamic parameters of linezolid in patients and selected the models to be used for the external validation. The bias of predictions was visually evaluated by plotting prediction errors (PEs) and relative PEs. The precision of prediction was evaluated by calculating the mean absolute error (MAE), root mean squared error (RMSE), and mean relative error (MRE). Results: Three articles (models A, B, and C) provided linezolid-induced platelet dynamic models using population pharmacokinetic and pharmacodynamic modeling approaches. The PE and relative PE of both linezolid concentrations and platelet counts for models A and C showed similar predictive distributions. With respect to the prediction accuracy of total linezolid concentration, the MAE, RMSE, and MRE of population prediction values for model C was the smallest. The comparison of the MAE, RMSE, and MRE of patient-individual prediction values for the 3 pharmacodynamic models revealed no large differences. Conclusions: We confirmed the transferability of published population pharmacokinetic and pharmacodynamic models and showed that they were suitable for extrapolation to other hospitals and/or patients. This study also introduced application software based on model C for the therapeutic drug monitoring of linezolid.